Cancer is a diverse set of diseases with vastly different genotypes and phenotypes. Nevertheless, angiogenesis (the formation of new blood vessels) plays an important role in the proliferation of cancer cells across cancer types. Indeed, the dependency of solid tumors on the growth of new blood vessels has made tumor blood vessels an appealing target for cancer therapy. Thus, cancer therapies that interfere with angiogenesis are being developed. For example, bevacizumab, a humanized monoclonal antibody against the vascular endothelial growth factor (VEGF), has been used to potentiate the effects of different active chemotherapeutic regimens.
To date, various agents that inhibit angiogenesis (e.g., endostatin, angiostatin, and thrombospondin) have been described. However, angiogenesis is important to normal physiological processes, such as growth and development or wound healing. Thus, current anti-angiogenesis therapies that do not discriminate between normal versus pathological angiogenesis, such as anti-VEGF monoclonal antibodies and tyrosine kinase receptor (TKR, also known as receptor tyrosine kinase (TKR)) inhibitors, suppress beneficial as well as pathological angiogenesis, by inducing systemic depression of cell signaling. For example, considering the vast biological role of VEGF in thyroid function, bone marrow function, immunomodulation, kidney function, vascular homeostasis, coagulation initiation, and physiological angiogenesis, the systematic suppression of VEGF can interfere will all of these essential functions.
Thus, there is a need for anti-angiogenesis therapies that discriminate between normal versus pathological angiogenesis.